The breast cancer scan developed by CRUK Cambridge Institute that could replace invasive tissue biopsies
An imaging technique that could replace the need for invasive tissue biopsies to determine quickly whether cancer treatments are working for an individual patient is being pioneered by University of Cambridge researchers, writes Paul Brackley.
The team’s latest findings on the technique have now been published in the journal Cancer Cell.
The research shows the technique – which involves magnetising molecules in a strong magnetic field – can be used to monitor how effective cancer drugs are at slowing tumour growth.
It exploits the process of our metabolism, by which cells break down glucose and other sugars to produce pyruvate, which is then converted into lactate. This is needed to produce energy and the building blocks for making new cells.
As tumours have a different metabolism to healthy cells, they produce more lactate.
A protein – FOXM1 – controls the production of a metabolic enzyme that converts pyruvate into lactate and also controls the production of many other proteins involved in cell growth and proliferation.
About 70 per cent of breast cancer cases are of a type known as estrogen-receptor (ER) positive and in many of these an enzyme known as PI3Ka is activated.
It leads to an abundance of FOXM1, which enables cancer cells to grow uncontrollably.
Drugs inhibiting PI3Ka are currently being tested in breast cancer patients, but they may not work for all as a patients’s tumour may have innate resistance to the drug, or develop it over time.
Dr Susana Ros, first author from the CRUK Cambridge Institute, said: “Thanks to advances in cancer treatments, our medicines are becoming more and more targeted, but not all drugs will work in every case – some tumours are resistant to particular drugs. What we need are biomarkers – biological signatures – that tell us whether a drug is working or not.”
The researchers grew breast cancer cells from patients in mouse ‘avatars’. Tumours resistant to P13Ka were able to continue producing FOXM1, making the molecule a biomarker for patients with this type of cancer.
While an invasive biopsy would usually be required to check if the inhibitor was working, the technique of hyperpolarisation prevents the need. It deploys a form of pyruvate with an additional neutron – carbon-13 molecules.
The carbon-13 pyruvate is then magnetised – or ‘hyperpolarised’ – by cooling to around one degree above absolute zero (-272C) and exposing it to extremely strong magnetic fields and microwave radiation.
The frozen material is thawed and dissolved into an injectable solution given to a patient as they undergo an MRI scan.
The signal strength from the hyperpolarised carbon-13 pyruvate molecules is 10,000 times stronger than from normal pyruvate, making them visible on the scan.
It demonstrates how fast pyruvate is being converted into lactate, which would require the continued presence of FOXM1. If this is seen, the drug is not working properly.
Dr Ros added: “We’ve been able to detect the presence of FOXM1, our biomarker, by using this new imaging technique in breast cancer models to look for a proxy – that is, how quickly pyruvate is converted to lactate.”
Professor Kevin Brindle , senior author of the study, said: “In the future, this could provide us with a rapid assessment of how a breast cancer patient is responding to treatment without the need for invasive biopsies.
“This information could help put an end to giving treatments that are not working and the side effects that accompany them. Currently, patients can wait a long time to find out if a treatment is working.
“This technique could shorten this time, and help to tailor treatment for individual patients.”